Key Points:
- NR and NMN have the best track record with no serious adverse side effects reported in human trials.
- Boosting NAD+ does not cause cancer.
- Boosting NAD+ could potentially contribute to the survival of inflammation-inducing cells, which could be mitigated with compounds called senolytics.
Boosting NAD+ can revitalize the NAD+ levels of particular individuals, including obese and older adults. Furthermore, restoring NAD+ can bring about an assortment of benefits connected to slowing aging. But are there any downsides? The following are the potential dangers associated with NAD+ and the NAD+ precursors niacin, nicotinamide, NR (nicotinamide riboside), and NMN (nicotinamide mononucleotide).
NAD+ Precursor Pitfalls
The preferred method of boosting NAD+ is with NAD+ precursors, at least for scientists like Harvard professor Dr. David Sinclair and Stanford professor Dr. Andrew Huberman. Moreover, Bryan Johnson, a millionaire devoted to reversing his aging, also supplements with NAD+ precursors on a daily basis.
The chief alternative to NAD+ precursors is intravenous (IV) NAD+ injections. However, many individuals find IV NAD+ therapy impractical. This is because it can be time-consuming and costly. NAD+ injections also come with dangers that do not apply to NAD+ precursors, including hazards associated with using a needle, as discussed here.
Niacin and Nicotinamide
A dose of the NAD+ precursor niacin (also known as vitamin B3) at 50 mg/kg or higher is associated with flushing and itching. While not serious, this side effect can be irritating to most individuals. Another NAD+ precursor, also discovered decades ago, is nicotinamide. A 250 mg dose of nicotinamide induces liver toxicity in animals and humans that can be reversed upon ceasing supplementation. Nicotinamide has also been shown to inhibit sirtuins, which are DNA-protection enzymes that carry out many of the beneficial effects of boosting NAD+.
NR and NMN
The NAD+ precursors NR and NMN were discovered more recently than niacin and nicotinamide and are not associated with flushing, itching, or liver toxicity. However, NR, NMN, and nicotinamide have been shown in animal studies to alter glucose metabolism. Side effects experienced by some subjects in nicotinamide, NR, and NMN human studies include diarrhea, nausea, rashes, calf cramps, skin burning, fatigue, headache, abdominal discomfort, and low platelet counts.
NAD+ and Cancer
NAD+ naturally occurs within all of our cells and is essential for cellular energy production, cell survival, and cell proliferation. It follows that boosting NAD+ indiscriminately restores the capacity of our cells to produce energy, survive, and proliferate. This means that boosting NAD+ could potentially rejuvenate cancer cells if they are already present in the body.
Importantly, boosting NAD+ does not cause cancer. However, boosting NAD+ could potentially maintain the survival and proliferation of cancer cells that have developed by other means. Accordingly, it is strongly suggested that those with a history or family history of cancer consult a healthcare practitioner before attempting to boost NAD+ levels via supplementation.
Furthermore, boosting NAD+ could potentially prevent the development of cancer by protecting our DNA from mutations. Therefore, choosing to supplement with NAD+ largely depends on the likelihood of having cancer cells in the body. Unfortunately, current medical technology does not allow for the detection of small groups of cancer cells.
NAD+ and Inflammation
One of the primary drivers of aging is inflammation, which is largely exacerbated by senescent cells. Likely as a result of immune system dysfunction, senescent cells accumulate with aging and secrete pro-inflammatory molecules. Considering that boosting NAD+ tends to indiscriminately target all the cells in our body, it could potentially keep senescent cells alive.
However, further research is needed, as the relationship between the immune system, senescent cells, and NAD+ works in a feed-forward loop. Still, senescent cells can be removed from the body with compounds called senolytics. Mayo Clinic scientists have even suggested combining NAD+ precursors with senolytics to reverse aging and prolong lifespan.
With that being said, there are already products on the market that combine NAD+ precursors with senolytics, including RESTORIN and NAD+ Triple Boost Ultra Nevertheless, RESTORIN is likely to promote higher senolytic activity.
The Best Bet
When it comes to the most effective NAD+ precursor with the least number of side effects, NMN and NR are the best choices. However, little is known about the long-term effects of NMN or NR supplementation. Longer studies will be needed to confirm the overall safety of NMN and NR that has previously been demonstrated in short-term studies.
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